抗苗勒氏管激素在多囊卵巢综合征患者行人工授精预测价值的评估
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摘要
【目的】评估抗苗勒氏管激素(AMH)水平对多囊卵巢综合征(PCOS)不孕患者的促排卵治疗、人工授精(IUI)妊娠结局、多卵泡发育或无优势卵泡发育而取消IUI周期的预测价值。【方法】回顾性分析了2014年1月至2017年8月,在中山大学孙逸仙纪念医院生殖中心因PCOS的不孕症患者行IUI助孕数据,按获得临床妊娠、未妊娠、因多卵泡发育或无优势卵泡发育而取消周期分为3组,分别比较各组之间各血清AMH、基础FSH及基础窦卵泡(AFC)等卵巢功能评价指标,并根据ROC曲线计算AMH预测多卵泡发育或无优势卵泡发育而取消周期及获得累积临床妊娠结局的cutoff值。【结果】PCOS患者中原发或继发性不孕、单纯排卵障碍或合并盆腔因素的临床妊娠率为15.9%～17.1%,而重复周期(≤3个周期)中,累积临床妊娠率上升为21.6%,较第1周期平均临床妊娠率(16.7%)显著升高。临床妊娠组、非妊娠组及取消周期组之间AMH、基础FSH、基础窦卵泡数(AFC)、外源促性腺激素(Gn)的刺激时间及Gn总剂量的差异具有统计学意义:取消周期组的AMH水平显著高于未取消周期组[(14.1±6.5)vs(10.3±4.3)ng/mL,(14.1±6.5)vs(9.3±4.3)ng/mL,P<0.025]。临床妊娠组、取消周期组和未妊娠组比较,前两者AFC平均值均显著增高[(34.5±11.4)vs(30.7±11.3),(7.8±10.8)vs(30.7±11.3),P<0.025]。另外,女方年龄、基础FSH与重复IUI周期累积妊娠率呈负相关,女性基础BMI、AFC以及AMH、HCG日成熟卵泡数与累积妊娠率呈正相关。AMH与HCG日成熟卵泡数可能是影响患者IUI累积临床妊娠的影响因素。通过ROC曲线分析,AMH较AFC更适合预测IUI周期取消风险及累积妊娠结局。【结论】重复实施IUI可提高PCOS不孕夫妻的IUI累积妊娠率,AMH作为衡量卵巢储备功能的重要指标,可用于预测IUI的临床妊娠、周期取消率:当AMH≥6.56 ng/mL时IUI的累积妊娠率增高,但当AMH≥14.72 ng/mL时,IUI因多卵泡发育或无优势卵泡发育而取消促排卵风险增高。
【Objective】To evaluate the role of serum antimullerian hormone(AMH)concentration in predicting clinical outcomes in controlled ovarian stimulation and intrauterine insemination(IUI). 【Methods】 A retrospective analysis of IUI data from patients with polycystic ovary syndrome and infertility in our reproductive center from January2014 to August 2017. According to the clinical outcomes,data was divided into three groups:clinical pregnancy group,non-pregnant group,and cancellation cycle group due to multiple follicular or no dominant follicular develop. The ovarian function evaluation indexes were compared such as serum AMH,basal FSH and basal sinus follicle(AFC). The cutoff values of the AMH to predict multi-follicular development or no dominant follicular development which IUI cycles were cancelled,and to predict obtain cumulative clinical pregnancy outcomes were calculated according to the ROC curve to cancel the cycle.【Results】 The clinical pregnancy rates of PCOS patients were from 15.9% to 17.1%,while the cumulative clinical pregnancy rate increased in repeat cycles(≤3 cycles)was 21.6%,significantly higher than the average clinical pregnancy rate(16.7%)during the first cycle. AMH levels in the cancelled cycle group were significantly higher than those in the non-cancelled cycle group[(14.1±6.5)vs(10.3±4.3)ng/mL,(14.1±6.5)vs(9.3±4.3)ng/mL,P<0.025]. Compared with the clinical pregnancy group,cancel cycle group and non-pregnant group,the mean AFC of the former two groups were significantly higher[(34.5±11.4)vs(30.7±11.3),(7.8±10.8)vs(30.7±11.3),P<0.025]. In addition,we found that women′s age,baseline FSH were negatively correlated with the cumulative pregnancy rate of repeated IUI cycles,and women′ s baseline BMI,baseline LH,AFC,and AMH were positively correlated with cumulative pregnancy rates. The number of mature follicles on the HCG triggering day,as well as the value of AMH,may be the influencing factor of IUI cumulative clinical pregnancy. By ROC curve analysis,we assume that AMH is more suitable than the AFC to predict IUI cycle cancellation rate and the cumulative pregnancy rate.【Conclusion】Repeated IUI cycles can be improved cumulative pregnancy rate of PCOS infertile couples. AMH,as an important index to measure ovarian reserve function,can be used to predict the the IUI cumulative clinical pregnancy outcomes and cancelled cycle rates:as AMH increased to more than 6.56 ng/mL,the pregnancy rate increased;but when AMH ≥14.72 ng/mL,the risk of cancelled IUI cycles was increased,becasues of multi-follicular developing and absence of dominant follicle development.
【Objective】To evaluate the role of serum antimullerian hormone(AMH)concentration in predicting clinical outcomes in controlled ovarian stimulation and intrauterine insemination(IUI). 【Methods】 A retrospective analysis of IUI data from patients with polycystic ovary syndrome and infertility in our reproductive center from January2014 to August 2017. According to the clinical outcomes,data was divided into three groups:clinical pregnancy group,non-pregnant group,and cancellation cycle group due to multiple follicular or no dominant follicular develop. The ovarian function evaluation indexes were compared such as serum AMH,basal FSH and basal sinus follicle(AFC). The cutoff values of the AMH to predict multi-follicular development or no dominant follicular development which IUI cycles were cancelled,and to predict obtain cumulative clinical pregnancy outcomes were calculated according to the ROC curve to cancel the cycle.【Results】 The clinical pregnancy rates of PCOS patients were from 15.9% to 17.1%,while the cumulative clinical pregnancy rate increased in repeat cycles(≤3 cycles)was 21.6%,significantly higher than the average clinical pregnancy rate(16.7%)during the first cycle. AMH levels in the cancelled cycle group were significantly higher than those in the non-cancelled cycle group[(14.1±6.5)vs(10.3±4.3)ng/mL,(14.1±6.5)vs(9.3±4.3)ng/mL,P<0.025]. Compared with the clinical pregnancy group,cancel cycle group and non-pregnant group,the mean AFC of the former two groups were significantly higher[(34.5±11.4)vs(30.7±11.3),(7.8±10.8)vs(30.7±11.3),P<0.025]. In addition,we found that women′s age,baseline FSH were negatively correlated with the cumulative pregnancy rate of repeated IUI cycles,and women′ s baseline BMI,baseline LH,AFC,and AMH were positively correlated with cumulative pregnancy rates. The number of mature follicles on the HCG triggering day,as well as the value of AMH,may be the influencing factor of IUI cumulative clinical pregnancy. By ROC curve analysis,we assume that AMH is more suitable than the AFC to predict IUI cycle cancellation rate and the cumulative pregnancy rate.【Conclusion】Repeated IUI cycles can be improved cumulative pregnancy rate of PCOS infertile couples. AMH,as an important index to measure ovarian reserve function,can be used to predict the the IUI cumulative clinical pregnancy outcomes and cancelled cycle rates:as AMH increased to more than 6.56 ng/mL,the pregnancy rate increased;but when AMH ≥14.72 ng/mL,the risk of cancelled IUI cycles was increased,becasues of multi-follicular developing and absence of dominant follicle development.
引文
[1]魏代敏,潘烨,石玉华.多囊卵巢综合征辅助生殖治疗策略的优化[J].中华妇产科杂志,2018(1):58-61.Wei DM,Pan Y,Shi YH. Optimization of assistedreproductive treatment strategies polycystic ovarysyndrome[J]. Chin J of Obst and Gynec,2018(1):58-61.
[2]谢言信,潘萍,林海燕,等.正常卵巢功能患者使用不同降调方案的临床研究[J].中山大学学报(医学版),2018,39(3):405-412.Xie YX,Pan P,Lin HY,et al. Three GnRHAgonist Protocols of Down Regulation on PituitarySuppression and Pregnancy Outcome of In VitroFertilization in Women with Normal OvarianReserve:A Randomized-Control Clinical Trial[J]. JSun Yat-sen Univ(Med Sci),2018,39(3):405-412.
[3] Shaban MM,Abdel MG. Role of ultrasonographicmarkers of ovarian reserve in prediction of IVF andICSI outcome[J]. Gynecol Endocrinol,2014,30(4):290-293.
[4] Weenen C,Laven JS,Von Bergh AR,et al. Anti-Mullerian hormone expression pattern in the humanovary:potential implications for initial and cyclicfollicle recruitment[J]. Mol Hum Reprod,2004,10(2):77-83.
[5] Das M, Gillott DJ, Saridogan E, et al. Anti-Mullerian hormone is increased in follicular fluidfrom unstimulated ovaries in women with polycysticovary syndrome[J]. Hum Reprod,2008,23(9):2122-2126.
[6] Pellatt L,Hanna L,Brincat M,et al. Granulosacell production of anti-Mullerian hormone isincreased in polycystic ovaries[J]. J ClinEndocrinol Metab,2007,92(1):240-245.
[7]王馥新,孟庆霞,邹琴燕,等.多囊卵巢综合征患者显著升高的抗苗勒管激素水平对超促排卵的影响[J].中华生殖与避孕杂志,2017(1):22-26.Wang FX,Meng QZ,Zou QY,et al. Comparison ofantiMüllerian hormone and ovarian responsebetween polycystic ovary syndrome patients andpatients with polycystic ovarian morphology[J].Chin J of Reprod and Contra,2017(1):22-26.
[8] Moghetti P. Insulin Resistance and Polycystic OvarySyndrome[J]. Curr Pharm Des,2016,22(36):5526-5534.
[9] Condorelli RA,Calogero AE,Di Mauro M,et al.PCOS and diabetes mellitus:from insulin resistanceto altered beta pancreatic function, a link inevolution[J]. Gynecol Endocrinol,2017,33(9):665-667.
[10]Abdalmageed OS,Farghaly TA,Abdelaleem AA,et al. Impact of Metformin on IVF Outcomes inOverweight and Obese Women With PolycysticOvary Syndrome:A Randomized Double-BlindControlled Trial[J]. Reprod Sci,2018:288055201.
[11]Sheng Y,Lu G,Liu J,et al. Effect of body massindex on the outcomes of controlled ovarianhyperstimulation in Chinese women with polycysticovary syndrome:a multicenter, prospective,observational study[J]. J Assist Reprod Genet,2017,34(1):61-70.
[12]Einarsson S,Bergh C,Friberg B,et al. Weightreduction intervention for obese infertile womenprior to IVF:a randomized controlled trial[J]. HumReprod,2017,32(8):1621-1630.
[13]Berkovitz A,Biron-Shental T,Pasternak Y,et al.Predictors of twin pregnancy after ovarianstimulation and intrauterine insemination in womenwith unexplained infertility[J]. Hum Fertil(Camb),2017,20(3):200-203.
[14]李轶,谭嘉琦,麦卓瑶,等.抗苗勒管激素水平对多囊卵巢综合征辅助生殖治疗结局的预测价值[J].中华妇产科杂志,2018(1):23-30.Li Y,Tan JQ,Mai ZY,et al. Value of anti-Müllerian hormone in predicting pregnant outcomesof polycystic ovary syndrome patients undergoneassisted reproductive technology[J]. Chin J ObstetGynecol,2018(1):23-30.
[2]谢言信,潘萍,林海燕,等.正常卵巢功能患者使用不同降调方案的临床研究[J].中山大学学报(医学版),2018,39(3):405-412.Xie YX,Pan P,Lin HY,et al. Three GnRHAgonist Protocols of Down Regulation on PituitarySuppression and Pregnancy Outcome of In VitroFertilization in Women with Normal OvarianReserve:A Randomized-Control Clinical Trial[J]. JSun Yat-sen Univ(Med Sci),2018,39(3):405-412.
[3] Shaban MM,Abdel MG. Role of ultrasonographicmarkers of ovarian reserve in prediction of IVF andICSI outcome[J]. Gynecol Endocrinol,2014,30(4):290-293.
[4] Weenen C,Laven JS,Von Bergh AR,et al. Anti-Mullerian hormone expression pattern in the humanovary:potential implications for initial and cyclicfollicle recruitment[J]. Mol Hum Reprod,2004,10(2):77-83.
[5] Das M, Gillott DJ, Saridogan E, et al. Anti-Mullerian hormone is increased in follicular fluidfrom unstimulated ovaries in women with polycysticovary syndrome[J]. Hum Reprod,2008,23(9):2122-2126.
[6] Pellatt L,Hanna L,Brincat M,et al. Granulosacell production of anti-Mullerian hormone isincreased in polycystic ovaries[J]. J ClinEndocrinol Metab,2007,92(1):240-245.
[7]王馥新,孟庆霞,邹琴燕,等.多囊卵巢综合征患者显著升高的抗苗勒管激素水平对超促排卵的影响[J].中华生殖与避孕杂志,2017(1):22-26.Wang FX,Meng QZ,Zou QY,et al. Comparison ofantiMüllerian hormone and ovarian responsebetween polycystic ovary syndrome patients andpatients with polycystic ovarian morphology[J].Chin J of Reprod and Contra,2017(1):22-26.
[8] Moghetti P. Insulin Resistance and Polycystic OvarySyndrome[J]. Curr Pharm Des,2016,22(36):5526-5534.
[9] Condorelli RA,Calogero AE,Di Mauro M,et al.PCOS and diabetes mellitus:from insulin resistanceto altered beta pancreatic function, a link inevolution[J]. Gynecol Endocrinol,2017,33(9):665-667.
[10]Abdalmageed OS,Farghaly TA,Abdelaleem AA,et al. Impact of Metformin on IVF Outcomes inOverweight and Obese Women With PolycysticOvary Syndrome:A Randomized Double-BlindControlled Trial[J]. Reprod Sci,2018:288055201.
[11]Sheng Y,Lu G,Liu J,et al. Effect of body massindex on the outcomes of controlled ovarianhyperstimulation in Chinese women with polycysticovary syndrome:a multicenter, prospective,observational study[J]. J Assist Reprod Genet,2017,34(1):61-70.
[12]Einarsson S,Bergh C,Friberg B,et al. Weightreduction intervention for obese infertile womenprior to IVF:a randomized controlled trial[J]. HumReprod,2017,32(8):1621-1630.
[13]Berkovitz A,Biron-Shental T,Pasternak Y,et al.Predictors of twin pregnancy after ovarianstimulation and intrauterine insemination in womenwith unexplained infertility[J]. Hum Fertil(Camb),2017,20(3):200-203.
[14]李轶,谭嘉琦,麦卓瑶,等.抗苗勒管激素水平对多囊卵巢综合征辅助生殖治疗结局的预测价值[J].中华妇产科杂志,2018(1):23-30.Li Y,Tan JQ,Mai ZY,et al. Value of anti-Müllerian hormone in predicting pregnant outcomesof polycystic ovary syndrome patients undergoneassisted reproductive technology[J]. Chin J ObstetGynecol,2018(1):23-30.
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